Influence of l-NAME -induced hypertension on spermatogenesis and sperm tsRNA profile in mice.

Sperm is the key media between the father's aberrant exposure and the offspring's phenotype. Whether paternal hypertension affects offspring through sperm epigenetics remains to be explored. To investigate the underlying mechanisms, we constructed a hypertensive mice model induced by drinking l-NAME and found that spermatocytes and spermatids in the testis were increased significantly after l-NAME treatment. The sequencing of sperm showed that tsRNA profiles changed with 315 tsRNAs (195 up-regulated and 120 down-regulated) altered. Meanwhile, KEGG pathway analysis showed that the target genes of these altered tsRNAs were involved in influencing some important signaling pathways, such as the cAMP signaling path, the mTOR signaling path, the Hippo signaling path, and the Ras signaling path. Bioinformatics of tsRNA-miRNA-mRNA pathway interactions revealed several ceRNA mechanisms, such as tsRNA-00051, the ceRNA of miR-128-1-5p, co-targeting Agap1. This study provides evidence for enriching and further understanding the pathophysiology and paternal epigenetic mechanisms of testicular reproduction, as well as contributing to a rethinking of the transgenerational reprogramming mechanisms of paternal exposure in hypertension.